A more detailed picture of the molecular and physiological processes underlying learning and memory (L&M) might give clues to pharmacological interventions that could alleviate the symptoms of normal and pathologic cognitive decline. Many theories of learning involve the unique architecture of the hippocampus, particularly the widely studied inputs to the CA1 pyramidal cell subfield. One of the most abundant proteins expressed in the brain, specifically in the hippocampus, is the calcium/calmodulin-dependent kinase II (CaMKII) which has unique biochemical properties as a frequency detector of oscillating calcium signals. Many studies support a role in L&M of long-term potentiation which is regulated by CaMKII in the CA1 region. The goal of this proposal is to examine the cellular and behavioral role of the alpha isoform of CaMKII selectively in CA1 pyramidal cells. Aim 1 of the study will be focused on determining the precise behavioral changes of mutant mice engineered with neural- specific, postnatal, and hippocampal CAI-restricted knockout of alpha- CaMKII. The second aim will be to determine the electrophysiologic mechanisms underlying these behavioral changes.